Full Steam Ahead with Remote Ischemic Conditioning for Stroke
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COMMENTARY
Full Steam Ahead with Remote Ischemic Conditioning for Stroke Richard F. Keep & Michael M. Wang & Jianming Xiang & Ya Hua & Guohua Xi
Received: 5 May 2014 / Revised: 11 July 2014 / Accepted: 14 July 2014 / Published online: 24 July 2014 # Springer Science+Business Media New York 2014
The finding that brief periods of ischemia can protect tissues from later ischemic damage (ischemic preconditioning, IPC; [1, 2]) has not only engendered much research into underlying mechanisms [3–5] but also debate as to how to translate these findings to the clinic [6–11]. This was a focus of the 2nd Translational Preconditioning meeting held in Miami in 2012 [12] and likely to be a major focus of the 3rd meeting to be hosted by Dr. John Zhang in Los Angeles in 2014. Although preconditioning can be induced by many stimuli other than ischemia [13, 14], the finding that brief periods of tissue ischemia can induce protection in other tissues (socalled remote ischemic preconditioning, RIPC) has generated the most clinical interest. Thus, for example, brief periods of limb ischemia may protect the brain and heart from later ischemic damage [15–18]. Because of relative simplicity (repeated inflation of a cuff around arm or leg) and perceived safety, this has become the stimulus of choice for examining whether preconditioning has clinical utility. This has led to a plethora of clinical trials, with Clinical Trials.gov currently listing 55 and 12 trials focused on cardio- and neuroprotection, respectively. It really is full steam ahead with RIPC, and there also trials of remote ischemic per- and R. F. Keep : M. M. Wang : J. Xiang : Y. Hua : G. Xi Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA M. M. Wang Department Neurology, University of Michigan, Ann Arbor, MI, USA R. F. Keep Department Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA R. F. Keep (*) R5018 Biomedical Science Research Building, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA e-mail: [email protected]
postconditioning (where the cuff is inflated during [19, 20] or after the ischemic event; [21]). In the brain, there has been discussion over the best neurological conditions in which to test RIPC [6–11], and clinical trials have focused on a range of conditions. Thus, there are those focusing on the effects of RIPC on neurological complications following cardiac surgery (NCT01835392; NCT00877305), neurosurgery (NCT00866489, NCT 01654666, NCT01175876), subarachnoid hemorrhage (NCT01158508, NCT01110239), and ischemic stroke (NCT 00975962, remote ischemic preconditioning; NCT01672515, remote ischemic postconditioning). While these trials have focused on relative short-term neuroprotection by RIPC, others have focused on the effects of RIPC in patients with underlying cerebrovascular disease, examining stroke occurrence and hemodynamic parameters (NCT01658306, NCT 01321749, and NCT01570231). Data on a number of these trials have now been published. Meng et al. [22] examined the effects
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